Large doses of red wine extract help fat mice stay healthy and live longer

Thursday

Nov 9, 2006 at 12:01 AMJun 25, 2009 at 11:42 AM

WASHINGTON - The chubby black mice ate the equivalent of a junk food diet. They should have gotten sick.

WASHINGTON - The chubby black mice ate the equivalent of a junk food diet. They should have gotten sick.They should have had blood sugar levels that were off the chart.

They should have been falling off their exercise rods. They should have died early.

But they didn't.

Most of those mice are still alive, spinning away on their exercise rods like skilled log rollers. Their ample insides look like normal healthy mice, just super-sized.

How'd they do it? Huge amounts of red wine extract, that good-for-you standby.

It's too early to know if such a miracle pill could work for people, but scientists are excited. Some called the findings "spectacular."

"You have to pinch yourself to make sure that this is all real, but the study involved 27 different researchers each of whom had a Eureka moment," said Dr. David Sinclair, the lead researcher of the mouse study published on-line Thursday in the journal Nature.

The study by Harvard Medical School and the National Institute on Aging shows that heavy doses of the red wine ingredient, resveratrol, lowers the rate of diabetes, liver problems and other fat-related ill effects in obese mice.

Fat-related deaths dropped 31 percent for obese mice on the supplement, compared to fat mice that got no treatment. The mice that got the wine extract also lived longer than expected, the study showed.

Other preliminary work still under way shows the wine ingredient has promise in extending the lives of normal-sized mice, too, said Sinclair, a pathology professor with Harvard Medical School.

He has a financial stake in the research. He is co-founder of a pharmaceutical firm, Sirtris Pharmaceuticals Inc. of Cambridge, Mass., which is testing to see if the extract can safely be used to treat people with diabetes.

For years, red wine has been linked to numerous health benefits. But the new study shows that mammals given ultrahigh doses of resveratrol can get the good effects of cutting calories without actually doing it.

"If we're right about this, it would mean you could have the benefit of restricting calories without having to feel hungry," Sinclair said. "It's the Holy Grail of aging research."

Even though he called the work "tantalizing," Dr. Howard Eisenson, director of the Duke University Diet and Fitness Center urged people not to get too excited.

"All of us who practice medicine have learned that we can't leap from studies in the lab - particularly in lab animals - to what will happen in humans," he said.

Resveratrol, produced when plants are under stress, is found in the skin of grapes and in other plants, including peanuts and some berries.

The 55 resveratrol-treated obese mice were on a high-calorie diet - what one scientist called a "McDonald's diet." Not only were they about as healthy as normal mice, they were also as agile and active on exercise equipment as their lean cousins, demonstrating a normal quality of life that was unexpected for such obese creatures, said study co-author Rafael de Cabo of the Institute on Aging.

"These fat old mice can perform as well on this skill test as young lean mice," Sinclair said.

The only major body measurement that didn't improve - aside from weight - was cholesterol, and that didn't seem to matter in the overall health of the mice, Sinclair said.

The study is so promising that the aging institute this week is strongly considering a repeat of the same experiment with rhesus monkeys, a closer match to humans, said institute director Dr. Richard Hodes.

Hodes cautions that it's too early for people to start taking non-regulated resveratrol supplements because safety issues haven't been adequately addressed.

Sirtris Pharmaceuticals is working on a high-dose resveratrol pill that unlike unregulated supplements on the market now, would be used as a drug and require Food and Drug Administration approval, said company chief executive officer Dr. Christoph Westphal. And that development and federal approval is about five years away, he said.

Sirtris is aiming the research at diseases of aging, which includes diabetes.

Sinclair's results are so promising that he rushed the study into the science journal while the obese mice are still alive, not waiting several more weeks or months until they die. That raises some issues, including specific figures about mortality, but is understandable, said outside experts. The obese mice still lived past the median age for mice of their weight.

Even would-be competitors are praising the study.

"It's a fairly spectacular result," said University of Wisconsin medical professor Dr. Richard Weindruch, who co-founded another biotech company that looks at the genetics of aging and drugs that could expand life spans. "People will go to McDonald's and afterwards they'll do super-sized resveratrol."

"This is fantastic," said Brown University molecular biology professor Stephen Helfand, who was the first reviewer for the journal Nature and not part of the team. "This is a historic landmark contribution."

Helfand said he won't be taking red wine extract supplements - but he has put his elderly parents on them. Such supplements are available at health food stores and on-line, but not at doses equivalent to what the mice in the experiment got - roughly equal to 100 bottles of wine a day in humans.

Mice, he said, are good initial test subjects for human drugs because their bodies function similarly to people in many ways. However, the differences between mouse and man can prove crucial, he said.

Sinclair also takes resveratrol supplements, although he doesn't recommend it for others.

Resveratrol works by spurring activity and regrowth in cells' mitochondria, which Sinclair called "the energy powerhouses of the cell."

Some scientists, such as Weindruch and Hodes, worry that the research may encourage people to forget about their diets and wait for a red wine cure-all that may never come.

"It's not an excuse to overeat," Sinclair said. But he added that for mice at least, this shows you can be "fat, happy, healthy and vigorous."